Numerous microbiologic and immunologic studies in humans and experimental animals have established Porphyromonas gingivalis as one of the major pathogens associated with periodontitis. It has been established that host immune responses to P. gingivalis include T cell-mediated production of antibodies which can be detected in serum, crevicular fluid and saliva. However, the relationship between systemic and mucosal responses, the Th cells stimulated and periodontitis is not clear. Thus, the overall objective of this proposal is to determine the systemic and mucosal immune responses induced by different strains of P. gingivalis, the role of Th cell subsets in these responses and finally their contribution to the disease process. These studies will use the Fischer rat as the experimental animal model. Specifically, we will determine: 1) if strains of P. gingivalis induce different systemic and mucosal antibody responses; 2) if different antigens of P. gingivalis and the route of immunization selectively stimulate distinct Th cell subsets; 3) the ability of naive versus P. gingivalis- primed Th cells to support protective humoral responses; and 4) the ability of different P. gingivalis antigens and immunization regimens to induce responses protective against disease. Animals will be challenged with P. gingivalis strains. Systemic and mucosal antibody responses will be assessed by ELISA and Western blot analysis. Destruction of alveolar bone will be determined by digital radiography. In other studies, rats will be immunized by different routes with P. gingivalis fimbriae, hemagglutinin, capsular polysaccharide or lipopolysaccharide. Serum and saliva will be collected prior to treatment and every other week throughout the experiment. The level and isotype of antibody will be assessed. Splenic and Peyer's patch Th cells will be isolated and characterize for surface markers by FACS and for cytokine production at the levels of mRNA and secreted protein. Antigen-specific Th cell subsets will be adoptively transferred to nude Fischer rats which will be challenged with P. gingivalis. Systemic and mucosal antibody responses and levels of alveolar bone loss will be assessed. These studies will determine the mechanisms by which antigen-specific T cells and their factors contribute to periodontal disease. Following a similar protocol, rats will be immunized with different P. gingivalis antigens and assessed for protection against disease. The results of these studies will provide a better understanding of the interactions between the immune system and P. gingivalis antigens that account for the disease process. Furthermore, the proposed investigations will provide a guide for future studies in humans for the development of vaccines against adult periodontitis.